Variant 17-15631669-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001348119.1(TRIM16):c.1061A>G(p.Lys354Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,660 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

TRIM16
NM_001348119.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.62

Variant links:

Genes affected

TRIM16 (HGNC:17241): (tripartite motif containing 16) The protein encoded by this gene is a tripartite motif (TRIM) family member that contains two B box domains and a coiled-coiled region that are characteristic of the B box zinc finger protein family. While it lacks a RING domain found in other TRIM proteins, the encoded protein can homodimerize or heterodimerize with other TRIM proteins and has E3 ubiquitin ligase activity. This gene is also a tumor suppressor and is involved in secretory autophagy. [provided by RefSeq, Jan 2017]

TRIM16 links:

ENSG00000251537 (HGNC:):

ENSG00000251537 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.17054349).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM16	NM_001348119.1 linkuse as main transcript	c.1061A>G	p.Lys354Arg	missense_variant	11/12	ENST00000649191.2	NP_001335048.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIM16	ENST00000649191.2 linkuse as main transcript	c.1061A>G	p.Lys354Arg	missense_variant	11/12		NM_001348119.1	ENSP00000497185.2		O95361-1
ENSG00000251537	ENST00000455584.2 linkuse as main transcript	c.1061A>G	p.Lys354Arg	missense_variant	5/17	2		ENSP00000402644.2		H0Y626

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251176

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135742

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000881

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461660

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727142

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000360

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 19, 2022

The c.1061A>G (p.K354R) alteration is located in exon 8 (coding exon 5) of the TRIM16 gene. This alteration results from a A to G substitution at nucleotide position 1061, causing the lysine (K) at amino acid position 354 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Benign

0.89

DEOGEN2

Benign

0.0057

.;.;.;T;T;T;T

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.29

FATHMM_MKL

Benign

0.34

LIST_S2

Benign

0.65

T;T;T;.;T;T;.

M_CAP

Benign

0.0032

MetaRNN

Benign

0.17

T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

.;.;.;L;.;L;L

PrimateAI

Benign

0.38

PROVEAN

Benign

-1.0

.;.;N;.;.;N;.

REVEL

Benign

0.038

Sift

Benign

0.17

.;.;T;.;.;T;.

Sift4G

Benign

0.24

T;T;T;T;T;T;.

Polyphen

0.017

.;.;B;B;.;B;B

Vest4

0.086

MutPred

0.38

Loss of methylation at K354 (P = 0.0145);.;.;Loss of methylation at K354 (P = 0.0145);.;Loss of methylation at K354 (P = 0.0145);Loss of methylation at K354 (P = 0.0145);

MVP

0.25

MPC

1.0

ClinPred

0.060

GERP RS

2.4

Varity_R

0.046

gMVP

0.28

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over